Biodegradable Particles for Selective TReg Cell Expansion
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Solution Overview
Problem
Current treatments for autoimmune diseases often rely on immunosuppressants that weaken the entire immune system, making patients vulnerable to infections, and the adoption of adoptive transfer of regulatory T cells is hindered by logistical and safety concerns, along with challenges in expanding antigen-specific TReg cells.
Innovation Solution
Development of biodegradable particles comprising a polyester blend, a protein that binds to immune cells, and a cytokine-antibody fusion protein, which selectively expand antigen-specific TReg cells by targeting IL-2Rα+ cells while avoiding IL-2Rβ, thereby promoting immune tolerance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If immunosuppressants are used to treat autoimmune diseases, then immune response to self-antigens is suppressed, but the entire immune system is weakened making patients vulnerable to infection
Solution Approach 1:
The patent applies local quality by creating antigen-specific TReg cells that target only self-antigens associated with autoimmune diseases, rather than suppressing the entire immune system. The TReg cells are engineered to recognize specific self-antigens through MHC class II molecules, providing localized immune tolerance only where needed while preserving overall immune system functionality and protection against infections.
Solution Approach 2:
The patent segments the immune suppression function by separating it from general immunosuppression. Instead of using broad immunosuppressants that affect all immune cells, the invention creates distinct antigen-specific TReg cells that independently suppress only the autoimmune response against specific self-antigens, leaving other immune functions intact.
2Object-affected harmful factors
If adoptive transfer of TReg cells is performed, then effector T cell activity is suppressed, but logistical and manufacturing issues arise along with safety and stability concerns
Solution Approach 1:
The patent enables self-service by allowing patients to generate their own antigen-specific TReg cells through in vitro expansion followed by adoptive transfer. The cells are engineered to recognize the patient's specific self-antigens, eliminating the need for complex external manufacturing processes and reducing safety concerns associated with allogeneic or xenogeneic cell transfers. The system leverages the patient's own immune system components to create therapeutic cells.
3Productivity
If antigen-specific TReg cells are expanded, then effector T cell suppression is enhanced, but the expansion process is challenging
Solution Approach 1:
The patent introduces an intermediary approach by using biodegradable particles as a delivery platform for cytokines and antigens during TReg cell expansion. These particles facilitate controlled release of growth factors and antigen presentation, creating optimal conditions for TReg cell proliferation without requiring complex culture systems or precise manual control of expansion parameters.
Solution Approach 2:
The patent applies parameter changes by utilizing biodegradable particles with controlled degradation rates to modulate the release of cytokines and antigens during TReg cell expansion. By adjusting particle composition, size, and degradation characteristics, the system optimizes growth factor availability and antigen presentation timing, thereby enhancing TReg cell expansion efficiency under controlled in vitro conditions.
Data Source
AI summary
The disclosure is directed to a biodegradable particle comprising a polyester or polyester blend, a first protein that binds to an immune cell, and a second protein that promotes proliferation and/or activation of immune cells, and a third soluble protein or small molecule encapsulated within the particle. The second protein is a fusion protein comprising at least a portion of an antibody and at least a portion of a cytokine (i.e., an immunocytokine). The disclosure also is directed to methods for treating a disease or condition in a subject (e.g., an autoimmune disease) comprising administering the aforementioned biodegradable particle to the subject.